Saquinavir



Better Known as: Invirase or Fortovase

 * Marketed By: Roche


 * Major Indication: Human Immunodeficiency Virus Infection


 * Drug Class: HIV Protease Inhibitor
 * Date of FDA Approval (Patent Expiration): 1995 (2010)


 * 2004 Sales: $100 Million
 * Importance: It was the first HIV Protease inhibitor to be approved by the FDA. Due to the rapidity with which HIV developed resistance to Saquinavir, Roche halted sales of Saquinavir monotreatments in favor of combination treatments with Ritonavir.
 * See Pharmaceutical Drugs for more information about other drugs and diseases.

Mechanism of Action
When HIV infects a host, it directs the synthesis of several polyproteins. The maturation of the virus to its infectious form requires that these polyproteins be cleaved to their component proteins by HIV Protease. The subunits of HIV Protease come together to form a catalytic tunnel capable of binding the nascent peptides and cleaving them into their mature form. Within this tunnel lies two Asp-Thr-Gly conserved sequences, which contain the catalytic Asp residues. These catalytic Asp residues carry out the hydrolytic cleavage of the polyprotein. Saquinavir binds very precisely to these conserved sequences within the HIV Protease tunnel, preventing the nascent polyproteins from entering. Unable to actively cleave the nascent proteins into their appropriate form, HIV is unable to mature and proliferate, allowing the patients immune system to fight off the infection more easily.

Drug Resistance
The biggest difficulty with treating HIV is the rapidity at which it mutates and becomes resistant to treatments. To view a comprehensive and interactive analysis of the mutations which confer drug resistance to HIV Protease, See: HIV Protease Inhibitor Resistance Profile